14-94309773-C-T

Variant names:

• chr14-94309773-C-T
• rs772942603
• NM_001756.4:c.847G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001756.4(SERPINA6):​c.847G>A​(p.Asp283Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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. D283E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SERPINA6 NM_001756.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

Genes affected

SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30119705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4	c.847G>A	p.Asp283Asn	missense_variant	Exon 3 of 5	ENST00000341584.4	NP_001747.3
SERPINA6	XM_047431827.1	c.1018G>A	p.Asp340Asn	missense_variant	Exon 3 of 5		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINA6	ENST00000341584.4	c.847G>A	p.Asp283Asn	missense_variant	Exon 3 of 5	1	NM_001756.4	ENSP00000342850.3
SERPINA6	ENST00000555056.1	n.*159G>A		non_coding_transcript_exon_variant	Exon 3 of 5	2		ENSP00000451045.1
SERPINA6	ENST00000555056.1	n.*159G>A		3_prime_UTR_variant	Exon 3 of 5	2		ENSP00000451045.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251056 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135714

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

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: 1461866 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Uncertain	0.097	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.28
Sift	Uncertain	0.028	D
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
Vest4		0.19
MutPred		0.50		Gain of MoRF binding (P = 0.0327);
MVP		0.89
MPC		0.12
ClinPred		0.18	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.40

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: rs772942603; hg19: chr14-94776110;