rs11125895

Variant names:

• chr2-61842223-T-C
• rs11125895
• NM_001201543.2:c.321A>G
• FAM161A p.Ile107Met

Your query was ambiguous. Multiple possible variants found:

• chr2-61842223-T-C
• chr2-61842223-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001201543.2(FAM161A):​c.321A>G​(p.Ile107Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,636 control chromosomes in the GnomAD database, including 28,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2167 hom., cov: 32)
  • Exomes 𝑓: 0.19 (26175 hom.)
• Consequence: FAM161A NM_001201543.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.41
• Publications: 28 publications found

Genes affected

FAM161A (HGNC:25808): (FAM161 centrosomal protein A) This gene belongs to the FAM161 family. It is expressed mainly in the retina. Mouse studies suggested that this gene is involved in development of retinal progenitors during embryogenesis, and that its activity is restricted to mature photoreceptors after birth. Mutations in this gene cause autosomal recessive retinitis pigmentosa-28. Alternatively spliced transcript variants have been identified.[provided by RefSeq, Jan 2011]

FAM161A Gene-Disease associations (from GenCC):

• retinitis pigmentosa 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012713075).
• BP6: Variant 2-61842223-T-C is Benign according to our data. Variant chr2-61842223-T-C is described in ClinVar as Benign. ClinVar VariationId is 336744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201543.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM161A	NM_001201543.2	MANE Select	c.321A>G	p.Ile107Met	missense	Exon 2 of 7	NP_001188472.1	Q3B820-3
	FAM161A	NM_032180.3		c.321A>G	p.Ile107Met	missense	Exon 2 of 6	NP_115556.2	Q3B820-1
	FAM161A	NR_037710.2		n.340A>G		non_coding_transcript_exon	Exon 2 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM161A	ENST00000404929.6	TSL:1 MANE Select	c.321A>G	p.Ile107Met	missense	Exon 2 of 7	ENSP00000385158.1	Q3B820-3
	FAM161A	ENST00000405894.3	TSL:1	c.321A>G	p.Ile107Met	missense	Exon 2 of 6	ENSP00000385893.3	Q3B820-1
	FAM161A	ENST00000456262.5	TSL:1	n.321A>G		non_coding_transcript_exon	Exon 2 of 6	ENSP00000396105.1	F8WCZ8

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24937 AN: 152084 Hom.: 2172 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.182 AC: 45380 AN: 249384 AF XY: 0.182

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.177

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.187

GnomAD4 exome AF: 0.188 AC: 274156 AN: 1460434 Hom.: 26175 Cov.: 32 AF XY: 0.187 AC XY: 136033 AN XY: 726616

African (AFR) AF: 0.137 AC: 4568 AN: 33446

American (AMR) AF: 0.199 AC: 8889 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 4041 AN: 26118

East Asian (EAS) AF: 0.196 AC: 7755 AN: 39664

South Asian (SAS) AF: 0.191 AC: 16468 AN: 86240

European-Finnish (FIN) AF: 0.150 AC: 7998 AN: 53402

Middle Eastern (MID) AF: 0.185 AC: 1067 AN: 5764

European-Non Finnish (NFE) AF: 0.191 AC: 212526 AN: 1110744

Other (OTH) AF: 0.180 AC: 10844 AN: 60332

GnomAD4 genome AF: 0.164 AC: 24933 AN: 152202 Hom.: 2167 Cov.: 32 AF XY: 0.162 AC XY: 12069 AN XY: 74398

African (AFR) AF: 0.128 AC: 5336 AN: 41526

American (AMR) AF: 0.167 AC: 2550 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3468

East Asian (EAS) AF: 0.184 AC: 952 AN: 5178

South Asian (SAS) AF: 0.191 AC: 923 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1539 AN: 10594

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12585 AN: 68008

Other (OTH) AF: 0.167 AC: 353 AN: 2114

Alfa AF: 0.180 Hom.: 8786

Bravo AF: 0.166

Asia WGS AF: 0.194 AC: 674 AN: 3478

EpiCase AF: 0.184

EpiControl AF: 0.194

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Retinitis pigmentosa 28 (2)
-	-	1	Retinal dystrophy (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.7
DANN	Benign	0.71
DEOGEN2	Benign	0.00031	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0013	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.4
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.081
Sift	Benign	0.30	T
Sift4G	Benign	0.29	T
Varity_R		0.057
gMVP		0.086
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11125895;

hg19: chr2-62069358;

COSMIC: COSV56764403;

COSMIC: COSV56764403;