6-2948407-C-G

Variant names:

• chr6-2948407-C-G
• NM_004568.6:c.1022G>C

Variant summary

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

The NM_004568.6(SERPINB6):​c.1022G>C​(p.Arg341Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: SERPINB6 NM_004568.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

Genes affected

SERPINB6 (HGNC:8950): (serpin family B member 6) The protein encoded by this gene is a member of the serpin (serine proteinase inhibitor) superfamily, and ovalbumin(ov)-serpin subfamily. It was originally discovered as a placental thrombin inhibitor. The mouse homolog was found to be expressed in the hair cells of the inner ear. Mutations in this gene are associated with nonsyndromic progressive hearing loss, suggesting that this serpin plays an important role in the inner ear in the protection against leakage of lysosomal content during stress, and that loss of this protection results in cell death and sensorineural hearing loss. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2010]

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
SERPINB6	NM_004568.6	c.1022G>C	p.Arg341Pro	missense_variant	Exon 7 of 7	ENST00000380539.7	NP_004559.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINB6	ENST00000380539.7	c.1022G>C	p.Arg341Pro	missense_variant	Exon 7 of 7	3	NM_004568.6	ENSP00000369912.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 8.99e-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	Uncertain	0.55
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;D;D;D;D;D;D;T;T;.;D;D;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.87	.;.;.;.;.;.;.;D;.;D;.;D;D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M;M;M;.;.;.;M;M;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.1	D;D;D;D;.;D;.;.;.;.;.;D;.
REVEL	Uncertain	0.59
Sift	Benign	0.15	T;T;T;T;.;T;.;.;.;.;.;T;.
Sift4G	Benign	0.23	T;T;T;T;.;T;.;T;.;.;.;T;.
Polyphen		0.75	P;P;P;P;P;P;P;.;.;.;P;P;.
Vest4		0.54
MutPred		0.50		Gain of catalytic residue at R341 (P = 0.0166);Gain of catalytic residue at R341 (P = 0.0166);Gain of catalytic residue at R341 (P = 0.0166);Gain of catalytic residue at R341 (P = 0.0166);Gain of catalytic residue at R341 (P = 0.0166);Gain of catalytic residue at R341 (P = 0.0166);Gain of catalytic residue at R341 (P = 0.0166);.;.;.;Gain of catalytic residue at R341 (P = 0.0166);Gain of catalytic residue at R341 (P = 0.0166);.;
MVP		0.95
MPC		0.53
ClinPred		0.91	D
GERP RS		2.9
Varity_R		0.83
gMVP		0.52

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: chr6-2948641;