rs1307899222

Variant names:

• chr1-25284746-A-C
• rs1307899222
• NM_016124.6:c.322A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-25284746-A-C
• chr1-25284746-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016124.6(RHD):​c.322A>C​(p.Ile108Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000797 in 1,254,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. I108V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: RHD NM_016124.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.668
• Publications: 0 publications found

Genes affected

RHD (HGNC:10009): (Rh blood group D antigen) The Rh blood group system is the second most clinically significant of the blood groups, second only to ABO. It is also the most polymorphic of the blood groups, with variations due to deletions, gene conversions, and missense mutations. The Rh blood group includes this gene, which encodes the RhD protein, and a second gene that encodes both the RhC and RhE antigens on a single polypeptide. The two genes, and a third unrelated gene, are found in a cluster on chromosome 1. The classification of Rh-positive and Rh-negative individuals is determined by the presence or absence of the highly immunogenic RhD protein on the surface of erythrocytes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RSRP1 (HGNC:25234): (arginine and serine rich protein 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21686083).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016124.6. 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
	RHD	NM_016124.6	MANE Select	c.322A>C	p.Ile108Leu	missense	Exon 2 of 10	NP_057208.3
	RHD	NM_001282871.2		c.322A>C	p.Ile108Leu	missense	Exon 2 of 9	NP_001269800.1	Q02161-4
	RHD	NM_001282870.1		c.322A>C	p.Ile108Leu	missense	Exon 2 of 9	NP_001269799.1	Q5XLT0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHD	ENST00000328664.9	TSL:1 MANE Select	c.322A>C	p.Ile108Leu	missense	Exon 2 of 10	ENSP00000331871.4	Q02161-1
	RHD	ENST00000342055.9	TSL:1	c.322A>C	p.Ile108Leu	missense	Exon 2 of 9	ENSP00000339577.5	Q02161-4
	RHD	ENST00000568195.5	TSL:1	c.322A>C	p.Ile108Leu	missense	Exon 2 of 9	ENSP00000456966.1	H3BT10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.97e-7 AC: 1 AN: 1254176 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 625582

African (AFR) AF: 0.00 AC: 0 AN: 32364

American (AMR) AF: 0.00 AC: 0 AN: 42700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23858

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00 AC: 0 AN: 80950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5294

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 928588

Other (OTH) AF: 0.00 AC: 0 AN: 53470

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.3
DANN	Benign	0.86
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.67
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.052
Sift	Benign	0.045	D
Sift4G	Benign	0.13	T
Polyphen		0.041	B
Vest4		0.32
MutPred		0.58		Loss of methylation at K105 (P = 0.0687)
MVP		0.19
MPC		0.10
ClinPred		0.10	T
GERP RS		1.8
Varity_R		0.10
gMVP		0.34
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1307899222; hg19: chr1-25611237;