rs768103524

Variant names:

• chr4-152975282-C-G
• rs768103524
• NM_001371116.1:c.1991C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-152975282-C-G
• chr4-152975282-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371116.1(FHDC1):​c.1991C>G​(p.Ser664Trp) 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 1,461,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. S664L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FHDC1 NM_001371116.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

Genes affected

FHDC1 (HGNC:29363): (FH2 domain containing 1) Predicted to enable actin binding activity and microtubule binding activity. Involved in Golgi ribbon formation; cilium assembly; and stress fiber assembly. Located in cilium and microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26106444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHDC1	NM_001371116.1	c.1991C>G	p.Ser664Trp	missense_variant	Exon 12 of 12	ENST00000511601.6	NP_001358045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHDC1	ENST00000511601.6	c.1991C>G	p.Ser664Trp	missense_variant	Exon 12 of 12	5	NM_001371116.1	ENSP00000427567.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461262 Hom.: 0 Cov.: 91 AF XY: 0.00000138 AC XY: 1 AN XY: 726940

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T;T
Eigen	Benign	-0.075
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M
PhyloP100		0.34
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.055
Sift	Benign	0.075	T;T
Sift4G	Uncertain	0.014	D;D
Polyphen		0.99	D;D
Vest4		0.42
MutPred		0.33		Loss of disorder (P = 0);Loss of disorder (P = 0);
MVP		0.30
MPC		0.58
ClinPred		0.90	D
GERP RS		3.4
Varity_R		0.089
gMVP		0.28
Mutation Taster		=93/7	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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs768103524; hg19: chr4-153896434;