9-15578931-A-T

Variant names:

• chr9-15578931-A-T
• rs763638459
• NM_173550.4:c.260A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173550.4(CCDC171):​c.260A>T​(p.Asp87Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,596 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC171 NM_173550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.96

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC171	NM_173550.4	c.260A>T	p.Asp87Val	missense_variant	Exon 4 of 26	ENST00000380701.8	NP_775821.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC171	ENST00000380701.8	c.260A>T	p.Asp87Val	missense_variant	Exon 4 of 26	1	NM_173550.4	ENSP00000370077.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461414 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727064

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.260A>T (p.D87V) alteration is located in exon 4 (coding exon 3) of the CCDC171 gene. This alteration results from a A to T substitution at nucleotide position 260, causing the aspartic acid (D) at amino acid position 87 to be replaced by a valine (V). 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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.053	T
Polyphen		0.95	P
Vest4		0.71
MutPred		0.24		Gain of MoRF binding (P = 0.0152);
MVP		0.29
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.21
gMVP		0.10

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

LitVar

Other links and lift over

dbSNP: rs763638459; hg19: chr9-15578929;