2-61825639-CTT-C

Variant names:

• chr2-61825639-CTT-C
• rs759062810
• NM_001201543.2:c.*814_*815delAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001201543.2(FAM161A):​c.*814_*815delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 376,962 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: FAM161A NM_001201543.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.432
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.*814_*815delAA		3_prime_UTR	Exon 7 of 7	NP_001188472.1	Q3B820-3
	FAM161A	NM_032180.3		c.*814_*815delAA		3_prime_UTR	Exon 6 of 6	NP_115556.2	Q3B820-1
	FAM161A	NR_037710.2		n.2760_2761delAA		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM161A	ENST00000404929.6	TSL:1 MANE Select	c.*814_*815delAA		3_prime_UTR	Exon 7 of 7	ENSP00000385158.1	Q3B820-3
	FAM161A	ENST00000405894.3	TSL:1	c.*814_*815delAA		3_prime_UTR	Exon 6 of 6	ENSP00000385893.3	Q3B820-1
	FAM161A	ENST00000456262.5	TSL:1	n.*2312_*2313delAA		non_coding_transcript_exon	Exon 6 of 6	ENSP00000396105.1	F8WCZ8

Frequencies

GnomAD3 genomes AF: 0.000261 AC: 37 AN: 141702 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000299

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000202

Gnomad OTH AF: 0.000530

GnomAD2 exomes AF: 0.0443 AC: 2255 AN: 50930 AF XY: 0.0449

Gnomad AFR exome AF: 0.0329

Gnomad AMR exome AF: 0.0453

Gnomad ASJ exome AF: 0.0513

Gnomad EAS exome AF: 0.0311

Gnomad FIN exome AF: 0.0670

Gnomad NFE exome AF: 0.0431

Gnomad OTH exome AF: 0.0395

GnomAD4 exome AF: 0.0198 AC: 4647 AN: 235274 Hom.: 0 AF XY: 0.0197 AC XY: 2679 AN XY: 135768

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0241 AC: 130 AN: 5388

American (AMR) AF: 0.0291 AC: 451 AN: 15488

Ashkenazi Jewish (ASJ) AF: 0.0306 AC: 248 AN: 8100

East Asian (EAS) AF: 0.0168 AC: 136 AN: 8074

South Asian (SAS) AF: 0.0197 AC: 901 AN: 45682

European-Finnish (FIN) AF: 0.0183 AC: 175 AN: 9570

Middle Eastern (MID) AF: 0.0305 AC: 24 AN: 786

European-Non Finnish (NFE) AF: 0.0181 AC: 2371 AN: 131270

Other (OTH) AF: 0.0193 AC: 211 AN: 10916

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000261 AC: 37 AN: 141688 Hom.: 0 Cov.: 31 AF XY: 0.000335 AC XY: 23 AN XY: 68662

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000154 AC: 6 AN: 38994

American (AMR) AF: 0.00 AC: 0 AN: 14066

Ashkenazi Jewish (ASJ) AF: 0.000299 AC: 1 AN: 3340

East Asian (EAS) AF: 0.00 AC: 0 AN: 4942

South Asian (SAS) AF: 0.00 AC: 0 AN: 4442

European-Finnish (FIN) AF: 0.00189 AC: 16 AN: 8444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.000202 AC: 13 AN: 64408

Other (OTH) AF: 0.000529 AC: 1 AN: 1890

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0130 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs759062810; hg19: chr2-62052774;