X-44540940-G-A

Variant names:

• chrX-44540940-G-A
• rs6610953
• NM_173794.4:c.185+1005C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173794.4(FUNDC1):​c.185+1005C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 110,349 control chromosomes in the GnomAD database, including 960 homozygotes. There are 4,637 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (960 hom., 4637 hem., cov: 22)
• Consequence: FUNDC1 NM_173794.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 4 publications found

Genes affected

FUNDC1 (HGNC:28746): (FUN14 domain containing 1) This gene encodes a protein with a FUN14 superfamily domain. The function of the encoded protein is not known. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FUNDC1	NM_173794.4	c.185+1005C>T		intron_variant	Intron 2 of 4	ENST00000378045.5	NP_776155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FUNDC1	ENST00000378045.5	c.185+1005C>T		intron_variant	Intron 2 of 4	1	NM_173794.4	ENSP00000367284.4
FUNDC1	ENST00000483115.1	n.360+1005C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 16423 AN: 110298 Hom.: 957 Cov.: 22

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0298

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.149 AC: 16445 AN: 110349 Hom.: 960 Cov.: 22 AF XY: 0.142 AC XY: 4637 AN XY: 32635

African (AFR) AF: 0.147 AC: 4473 AN: 30353

American (AMR) AF: 0.0834 AC: 860 AN: 10314

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 320 AN: 2623

East Asian (EAS) AF: 0.192 AC: 668 AN: 3476

South Asian (SAS) AF: 0.164 AC: 429 AN: 2615

European-Finnish (FIN) AF: 0.164 AC: 940 AN: 5731

Middle Eastern (MID) AF: 0.0280 AC: 6 AN: 214

European-Non Finnish (NFE) AF: 0.159 AC: 8387 AN: 52847

Other (OTH) AF: 0.139 AC: 209 AN: 1503

Alfa AF: 0.152 Hom.: 14060

Bravo AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.60
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6610953; hg19: chrX-44400186;