rs12770830

Variant names:

• chr10-14842510-G-A
• rs12770830
• NM_001378785.1:c.226G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378785.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSANTD7	NM_001378785.1	MANE Select	c.226G>A	p.Ala76Thr	missense	Exon 4 of 5	NP_001365714.1	A0A1W2PQ72
	HSPA14	NM_016299.4	MANE Select	c.221+2353G>A		intron	N/A	NP_057383.2	Q0VDF9
	MSANTD7	NM_001378790.1		c.-80-861G>A		intron	N/A	NP_001365719.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSANTD7	ENST00000640019.3	TSL:1 MANE Select	c.226G>A	p.Ala76Thr	missense	Exon 4 of 5	ENSP00000491568.1	A0A1W2PQ72
	HSPA14	ENST00000378372.8	TSL:1 MANE Select	c.221+2353G>A		intron	N/A	ENSP00000367623.3	Q0VDF9
	HSPA14	ENST00000441647.1	TSL:3	c.185+2353G>A		intron	N/A	ENSP00000404691.1	H7C2A1

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

GnomAD2 exomes AF: 0.0773 AC: 10590 AN: 137034 AF XY: 0.0788

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 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

African (AFR) AF: 0.0185 AC: 583 AN: 31594

American (AMR) AF: 0.0812 AC: 2900 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.0841 AC: 2119 AN: 25182

East Asian (EAS) AF: 0.00215 AC: 77 AN: 35734

South Asian (SAS) AF: 0.0836 AC: 6620 AN: 79230

European-Finnish (FIN) AF: 0.0636 AC: 2155 AN: 33886

Middle Eastern (MID) AF: 0.126 AC: 716 AN: 5696

European-Non Finnish (NFE) AF: 0.0951 AC: 102650 AN: 1078864

Other (OTH) AF: 0.0817 AC: 4733 AN: 57906

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

African (AFR) AF: 0.0197 AC: 818 AN: 41538

American (AMR) AF: 0.0809 AC: 1237 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5180

South Asian (SAS) AF: 0.0711 AC: 343 AN: 4824

European-Finnish (FIN) AF: 0.0653 AC: 692 AN: 10598

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0964 AC: 6558 AN: 67998

Other (OTH) AF: 0.0796 AC: 168 AN: 2110

Alfa AF: 0.0866 Hom.: 1290

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 v4.9

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
PhyloP100		4.8
PrimateAI	Uncertain	0.70	T
GERP RS		5.9
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12770830; hg19: chr10-14884509;