9-15578892-T-G

Variant names:

• chr9-15578892-T-G
• rs115940611
• NM_173550.4:c.221T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173550.4(CCDC171):​c.221T>G​(p.Val74Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V74A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CCDC171 NM_173550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.73
• Publications: 4 publications found

Genes affected

CCDC171 (HGNC:29828): (coiled-coil domain containing 171)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39433643).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173550.4. 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
	CCDC171	NM_173550.4	MANE Select	c.221T>G	p.Val74Gly	missense	Exon 4 of 26	NP_775821.2
	CCDC171	NM_001355547.1		c.221T>G	p.Val74Gly	missense	Exon 3 of 25	NP_001342476.1	Q6TFL3-4
	CCDC171	NM_001348002.2		c.-221T>G		5_prime_UTR	Exon 4 of 27	NP_001334931.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC171	ENST00000380701.8	TSL:1 MANE Select	c.221T>G	p.Val74Gly	missense	Exon 4 of 26	ENSP00000370077.3	Q6TFL3-1
	CCDC171	ENST00000905141.1		c.221T>G	p.Val74Gly	missense	Exon 4 of 26	ENSP00000575200.1
	CCDC171	ENST00000971281.1		c.221T>G	p.Val74Gly	missense	Exon 4 of 26	ENSP00000641340.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251044 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461578 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727108

African (AFR) AF: 0.0000299 AC: 1 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111858

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.46
MutPred		0.35		Loss of stability (P = 0.0086)
MVP		0.28
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.65
gMVP		0.17
Mutation Taster		=90/10	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: rs115940611; hg19: chr9-15578890;