14-73934270-C-T

Variant names:

• chr14-73934270-C-T
• rs369764532
• NM_152445.3:c.1930G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152445.3(FAM161B):​c.1930G>A​(p.Val644Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,610,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V644L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: FAM161B NM_152445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 0 publications found

Genes affected

FAM161B (HGNC:19854): (FAM161 centrosomal protein B) Predicted to be involved in cilium organization. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000258891 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054343462).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152445.3. 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
	FAM161B	NM_152445.3	MANE Select	c.1930G>A	p.Val644Ile	missense	Exon 9 of 9	NP_689658.3	Q96MY7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM161B	ENST00000286544.5	TSL:1 MANE Select	c.1930G>A	p.Val644Ile	missense	Exon 9 of 9	ENSP00000286544.4	Q96MY7-1
	ENSG00000258891	ENST00000555916.1	TSL:1	n.407+1679G>A		intron	N/A
	FAM161B	ENST00000651776.1		c.2119G>A	p.Val707Ile	missense	Exon 9 of 9	ENSP00000499021.1	Q96MY7-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151998 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 249356 AF XY: 0.0000371

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.0000295

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000370 AC: 54 AN: 1458962 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 725818

African (AFR) AF: 0.0000300 AC: 1 AN: 33328

American (AMR) AF: 0.0000454 AC: 2 AN: 44056

Ashkenazi Jewish (ASJ) AF: 0.0000795 AC: 2 AN: 25156

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 85962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111438

Other (OTH) AF: 0.0000665 AC: 4 AN: 60184

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151998 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74252

African (AFR) AF: 0.0000241 AC: 1 AN: 41426

American (AMR) AF: 0.0000655 AC: 1 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3340

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.3
DANN	Benign	0.61
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.97	T
PhyloP100		0.32
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.043
Sift	Benign	0.15	T
Sift4G	Benign	0.10	T
Vest4		0.028
MVP		0.16
MPC		0.053
ClinPred		0.023	T
GERP RS		-2.8
Mutation Taster		=95/5	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: rs369764532; hg19: chr14-74400973; COSMIC: COSV54102766; COSMIC: COSV54102766;