NM_030943.4:c.1257+10C>T

Variant names:

• chr14-102930503-C-T
• rs386834166
• NM_030943.4:c.1257+10C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_030943.4(AMN):​c.1257+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000845 in 1,538,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1
• Conservation: PhyloP100: -4.32
• Publications: 1 publications found

Genes affected

AMN (HGNC:14604): (amnion associated transmembrane protein) The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [provided by RefSeq, Jul 2008]

AMN Gene-Disease associations (from GenCC):

• Imerslund-Grasbeck syndrome type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Imerslund-Grasbeck syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-102930503-C-T is Benign according to our data. Variant chr14-102930503-C-T is described in ClinVar as Benign. ClinVar VariationId is 56747.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00000794 (11/1385958) while in subpopulation MID AF = 0.00149 (7/4700). AF 95% confidence interval is 0.000699. There are 0 homozygotes in GnomAdExome4. There are 5 alleles in the male GnomAdExome4 subpopulation. Median coverage is 36. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.1257+10C>T		intron_variant	Intron 11 of 11	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.1095+10C>T		intron_variant	Intron 11 of 11		NP_001412175.1
AMN	XM_011537203.4	c.1095+10C>T		intron_variant	Intron 11 of 11		XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.1257+10C>T		intron_variant	Intron 11 of 11	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152110 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000152 AC: 2 AN: 131752 AF XY: 0.0000139

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000432

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000794 AC: 11 AN: 1385958 Hom.: 0 Cov.: 36 AF XY: 0.00000732 AC XY: 5 AN XY: 683248

African (AFR) AF: 0.0000320 AC: 1 AN: 31220

American (AMR) AF: 0.00 AC: 0 AN: 35348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24766

East Asian (EAS) AF: 0.00 AC: 0 AN: 35490

South Asian (SAS) AF: 0.00 AC: 0 AN: 78658

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42612

Middle Eastern (MID) AF: 0.00149 AC: 7 AN: 4700

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1075642

Other (OTH) AF: 0.0000174 AC: 1 AN: 57522

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74410

African (AFR) AF: 0.0000241 AC: 1 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67982

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000869 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Imerslund-Grasbeck syndrome Pathogenic:1 Benign:1

Oct 04, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.31
DANN	Benign	0.92
PhyloP100		-4.3

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: rs386834166; hg19: chr14-103396840;