chr10-32451911-A-T

Variant names:

• chr10-32451911-A-T
• NM_001395015.1:c.269A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395015.1(CCDC7):​c.269A>T​(p.His90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,738 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. H90R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCDC7 NM_001395015.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

Genes affected

CCDC7 (HGNC:26533): (coiled-coil domain containing 7)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24944046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC7	NM_001395015.1	c.269A>T	p.His90Leu	missense_variant	Exon 2 of 44	ENST00000639629.2	NP_001381944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC7	ENST00000639629.2	c.269A>T	p.His90Leu	missense_variant	Exon 2 of 44	5	NM_001395015.1	ENSP00000491655.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458738 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725316

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.11	.;.;T;T;T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.092
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.80	.;T;T;T;T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.25	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M;M;.;.;.;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-5.6	D;D;D;D;D;.
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D;D;D;D;.
Sift4G	Uncertain	0.015	D;D;D;D;D;.
Polyphen		0.98, 0.99	.;.;D;.;.;D
Vest4		0.63
MutPred		0.25		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.71
MPC		0.32
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.11
gMVP		0.084

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: chr10-32740839;