chr14-73934333-C-G

Position:

• chr14-73934333-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152445.3(FAM161B):​c.1867G>C​(p.Glu623Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FAM161B NM_152445.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0840

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050688893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM161B	NM_152445.3	c.1867G>C	p.Glu623Gln	missense_variant	9/9	ENST00000286544.5	NP_689658.3
FAM161B	XM_011536475.3	c.1867G>C	p.Glu623Gln	missense_variant	9/10		XP_011534777.2
FAM161B	XR_007063990.1	n.1935G>C		non_coding_transcript_exon_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM161B	ENST00000286544.5	c.1867G>C	p.Glu623Gln	missense_variant	9/9	1	NM_152445.3	ENSP00000286544.4
ENSG00000258891	ENST00000555916.1	n.407+1616G>C		intron_variant		1
FAM161B	ENST00000651776.1	c.2056G>C	p.Glu686Gln	missense_variant	9/9			ENSP00000499021.1
FAM161B	ENST00000556794.5	c.386+1616G>C		intron_variant		3		ENSP00000450889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2024

The c.2056G>C (p.E686Q) alteration is located in exon 9 (coding exon 9) of the FAM161B gene. This alteration results from a G to C substitution at nucleotide position 2056, causing the glutamic acid (E) at amino acid position 686 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.89
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.060
Sift	Benign	0.25	T
Sift4G	Benign	0.21	T
Vest4		0.060
MVP		0.17
MPC		0.064
ClinPred		0.060	T
GERP RS		2.0

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-74401036;