rs12770830

chr10-14842510-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378785.1(MSANTD7):c.226G>A(p.Ala76Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0864 in 1,536,000 control chromosomes in the GnomAD database, including 6,332 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.067 (442 hom., cov: 33)
  • Exomes 𝑓: 0.089 (5890 hom.)
• Consequence: MSANTD7 NM_001378785.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84

Genes affected

MSANTD7 (HGNC:56248): (Myb/SANT DNA binding domain containing 7)

HSPA14 (HGNC:29526): (heat shock protein family A (Hsp70) member 14) Predicted to enable several functions, including ATP binding activity; misfolded protein binding activity; and unfolded protein binding activity. Predicted to be involved in several processes, including cellular response to unfolded protein; chaperone cofactor-dependent protein refolding; and protein refolding. Located in cytosol. Colocalizes with ribosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003213048).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSANTD7	NM_001378785.1	c.226G>A	p.Ala76Thr	missense_variant	4/5	ENST00000640019.3
HSPA14	NM_016299.4	c.221+2353G>A		intron_variant		ENST00000378372.8
MSANTD7	NM_001378790.1	c.-80-861G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSANTD7	ENST00000640019.3	c.226G>A	p.Ala76Thr	missense_variant	4/5	1	NM_001378785.1	P1
HSPA14	ENST00000378372.8	c.221+2353G>A		intron_variant		1	NM_016299.4	P1
HSPA14	ENST00000441647.1	c.187+2353G>A		intron_variant		3
MSANTD7	ENST00000645667.1	n.323-861G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0672 AC: 10213 AN: 152090 Hom.: 442 Cov.: 33

Gnomad AFR AF: 0.0197

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0964

Gnomad OTH AF: 0.0790

GnomAD3 exomes AF: 0.0773 AC: 10590 AN: 137034 Hom.: 469 AF XY: 0.0788 AC XY: 5869 AN XY: 74506

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.0804

Gnomad ASJ exome AF: 0.0842

Gnomad EAS exome AF: 0.00238

Gnomad SAS exome AF: 0.0822

Gnomad FIN exome AF: 0.0651

Gnomad NFE exome AF: 0.0958

Gnomad OTH exome AF: 0.0805

GnomAD4 exome AF: 0.0886 AC: 122553 AN: 1383792 Hom.: 5890 Cov.: 32 AF XY: 0.0890 AC XY: 60763 AN XY: 682836

Gnomad4 AFR exome AF: 0.0185

Gnomad4 AMR exome AF: 0.0812

Gnomad4 ASJ exome AF: 0.0841

Gnomad4 EAS exome AF: 0.00215

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.0636

Gnomad4 NFE exome AF: 0.0951

Gnomad4 OTH exome AF: 0.0817

GnomAD4 genome AF: 0.0671 AC: 10216 AN: 152208 Hom.: 442 Cov.: 33 AF XY: 0.0670 AC XY: 4984 AN XY: 74408

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0809

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0653

Gnomad4 NFE AF: 0.0964

Gnomad4 OTH AF: 0.0796

Alfa AF: 0.0915 Hom.: 960

Bravo AF: 0.0644

TwinsUK AF: 0.0922 AC: 342

ALSPAC AF: 0.0955 AC: 368

ExAC AF: 0.0670 AC: 1224

Asia WGS AF: 0.0380 AC: 134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	24
Dann	Benign	0.83
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0032	T
MutationTaster	Benign	9.4e-27	P;P;P
PrimateAI	Uncertain	0.70	T
GERP RS		5.9

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: rs12770830; hg19: chr10-14884509;