7-22492671-T-C

Variant names:

• chr7-22492671-T-C
• NM_001382447.1:c.656A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001382447.1(STEAP1B):​c.656A>G​(p.Tyr219Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: STEAP1B NM_001382447.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.98

Genes affected

STEAP1B (HGNC:41907): (STEAP family member 1B) Predicted to be integral component of membrane. Predicted to be active in endosome and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STEAP1B	NM_001382447.1	c.656A>G	p.Tyr219Cys	missense_variant	Exon 4 of 5	ENST00000678116.1	NP_001369376.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STEAP1B	ENST00000678116.1	c.656A>G	p.Tyr219Cys	missense_variant	Exon 4 of 5		NM_001382447.1	ENSP00000503251.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461378 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727006

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: 9.00e-7

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	Benign	0.30
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;.;D
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.096
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.6	M;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.9	D;D;D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.82
MutPred		0.72		Loss of catalytic residue at I199 (P = 0.0769);.;.;
MVP		0.82
MPC		3.3
ClinPred		1.0	D
GERP RS		1.1
Varity_R		0.74
gMVP		0.93

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: chr7-22532290;